THB335

THB335 is a next-generation, oral, small molecule inhibitor of the receptor tyrosine kinase KIT (also known as c-KIT), developed by Third Harmonic Bio. It is designed to be a highly potent and selective inhibitor targeting KIT, which acts as the master regulator of mast cell function and survival. By inhibiting KIT, THB335 aims to reduce mast cell activation and associated inflammatory responses. The drug was structurally modified from its predecessor (THB001) to retain potency while improving safety—specifically addressing hepatotoxicity concerns observed with earlier compounds. THB335 has demonstrated dose-dependent reductions in serum tryptase (a biomarker of mast cell activation) in Phase 1 studies involving healthy volunteers, supporting its potential for treating chronic spontaneous urticaria and other mast-cell-mediated inflammatory diseases. As of early 2025, it has completed Phase 1 trials with plans for a Phase 2 trial in chronic spontaneous urticaria[1][2][3][4][5][6][8].